Development of a new approach for the synthesis of (+)-15-deoxy-Δ12,14-prostaglandin J2 methyl ester based on the [2+2]-cycloadduct of 5-trimethylsilylcyclopentadiene and dichloroketene

An asymmetric total synthesis of 15-deoxy-Δ12,14-prostaglandin J2 methyl ester is presented. The synthesis begins with the preparation of enantiopure (3aR,6R,6aS)-6-(trimethylsilyl)-3,3a,6,6a-tetrahydro-1H-cyclopenta[c]furan-1-one by optical resolution of the [2+2]-cycloadduct of the easily availabl...

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Bibliographic Details
Published in:New journal of chemistry 2022-01, Vol.46 (14), p.6708-6714
Main Authors: Gimazetdinov, Airat M, Aidar Z Al’mukhametov, Miftakhov, Mansur S
Format: Article
Language:English
Subjects:
Alkylation
Cascade chemical reactions
Chains
Cyclopentene
Dehydration
Synthesis
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Summary:An asymmetric total synthesis of 15-deoxy-Δ12,14-prostaglandin J2 methyl ester is presented. The synthesis begins with the preparation of enantiopure (3aR,6R,6aS)-6-(trimethylsilyl)-3,3a,6,6a-tetrahydro-1H-cyclopenta[c]furan-1-one by optical resolution of the [2+2]-cycloadduct of the easily available 5-trimethylcyclopentadiene and dichloroketene in situ. The key steps of the approach: (a) formation of cyclopentenone precursor by the consecutive epoxydation and Peterson-type fragmentation reactions of an allylic TMS-derivative of a suitable cyclopentene intermediate; (b) two-stage construction of the prostaglandin α-chain by Wittig olefinations; (c) alkylation using E-1-lithioheptene with subsequent ω-chain formation by generation of a cross-conjugated system by tandem deprotection and dehydration reactions.
ISSN:1144-0546
1369-9261
DOI:10.1039/d2nj01003h